Imma Perfetto
Cosmos science journalist
In research that might one day lead to solutions to some rare genetic abnormalities, scientists in China have successfully raised offspring from 2 male mice.
The stem cell scientists introduced mutations in a particular set of genetic locations to overcome the hurdles preventing unisexual reproduction in mammals.
They created offspring from 2 male mice by modifying 20 key “imprinting genes” that usually cause developmental abnormalities when they all come from the same sex.
Zhi-Kun Li, from the Chinese Academy of Science (CAS), says: “This work will help to address a number of limitations in stem cell and regenerative medicine research.”
Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning.
Some reptiles, amphibians, and fish can reproduce unisexually. For example, all-female species produce eggs which develop into clones of the mother in a process known as parthenogenesis.
But unisexual reproduction doesn’t occur in mammals without a lot of help from scientists. In the past, scientists have successfully produced fertile bi-maternal mice – with 2 mums and no dads – that survived until adulthood. In contrast, bi-paternal mice usually only develop to a certain point and then stop growing.
Most of the offspring in these tests also died young.
“The unique characteristics of imprinting genes have led scientists to believe that they are a fundamental barrier to unisexual reproduction in mammals,” says co-corresponding author Qi Zhou, from CAS.
“Even when constructing bi-maternal or bi-paternal embryos artificially, they fail to develop properly, and they stall at some point during development due to these genes.”
In diploid organisms, like humans and mice, every non-reproductive cell of the body contains 2 copies of the genome, one inherited from each parent at fertilisation. This means there are 2 copies, or alleles, of every gene on non-sex chromosomes.
Genome imprinting is a process that causes certain alleles to be expressed, or not, depending on whether they were inherited from the maternal or paternal parent.
This process happens during egg or sperm formation and remains for the lifetime of that individual.
The problem with producing offspring from parents of the same sex is that genome imprinting becomes unbalanced. An over- or under-expression of maternal and paternal imprinted genes causes severe developmental defects.
In the latest study, which appears in the journal Cell Stem Cell, researchers introduced modifications to 20 key imprinting genes in bi-paternal mouse embryos and found that 11.8% of them developed until birth.
Due to developmental defects, not all pups that were born lived to adulthood and most that did were sterile, had altered growth, and a shortened lifespan. The team will continue to study how modifying imprinting genes may lead to healthier embryos.
“Further modifications to the imprinting genes could potentially facilitate the generation of healthy bi-paternal mice capable of producing viable gametes [sperm] and lead to new therapeutic strategies for imprinting-related diseases,” says co-corresponding author Zhi-Kun Li of CAS.
Human disorders involving genomic imprinting include Angelman syndrome, Prader–Willi syndrome, and Beckwith–Wiedemann syndrome.
The team also plans to extend their experiments to larger animals, including monkeys. However, this will require considerable time and effort because imprinting gene combinations in monkeys are significantly different to those in mice.
